Synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives

A new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against Leishmania donovani and Trypanosoma brucei brucei. Results from these structure–activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against L. donovani promastigotes and amastigotes parasites (IC50 values in a range of 2–11 μM). Additionally, compound 3b has emerged from this study as the most active compound in the series against T. b. brucei with a MEC value of 12 μM. These three compounds are worth of further in vivo evaluation.

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► 3-substituted quinolinones derivatives have been synthesized.
► Activity is noticeably influenced by the substituent at the C3 of the quinolinone.
► Compounds 3a and 4g exert similar biological profile as miltefosine.
► Compounds 3b exerts similar biological profile as the reference compounds pentamidine.